HLA-DQ6-mediated protection in IDDM

Insulin-dependent diabetes mellitus is positively associated with DQ8, DQ2, and DQ6 (DQB1*0604), and negatively associated with DQ6 (DQB1*0602), DQ6 ( DQB1*0603), and DQ7 in Swedish caucasians. The protection conferred by DQ6 (DQB1*0602) is stronger in younger individuals and there is decrease in the effect of protection with increasing age. Three-dimensional modeling of th e susceptible DQ6 (DQB1*0604) and protective DQ6 (DQB1*0602), which share t he same DQA chain (DQA1*0102) but differ in the DQB chain at 6 residues, id entifies residue 57 and 70 to be important for protection. Three-dimensiona l models of the DQ8 molecules were constructed from the coordinates of the DR1 crystal structure and other susceptibility and resistance molecules wer e made by homology modeling. The positively associated DQ molecules had wea kly negative ro significantly positive surface electrostatic potentials ove r the peptide binding and T cell recognition areas, whereas the negatively associated molecules had distinctly more negative areas over the relevant s urface. This suggests that the variation in the physicochemical properties such as molecular electrostatic potentials among different DQ molecules are important. Human Immunology 61, 148-153 (2000). (C) American Society for H istocompatibility and Immunogenetics, 2000. Published by Elsevier Science I nc.